Fatigue in Post-COVID-Condition is accompanied by hypoperfusion of right-occipital areas, 2025, Hosp et al.

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Fatigue in Post-COVID-Condition is accompanied by hypoperfusion of right-occipital areas

Spoiler: Authors

Jonas A Hosp; Nils Schröter; Marco Reisert; Sibylle Frase; Elias Kellner; Hansjörg Mast; Cornelius Weiller; Horst Urbach; Alexander Rau

BACKGROUND AND PURPOSE
A proportion of individuals recovering from COVID-19 continue to experience persistent symptoms, including fatigue and cognitive difficulties — a syndrome commonly referred to as Post-COVID condition (PCC), which affects an estimated 2–10% of cases. In this study, we evaluated cerebral blood flow (CBF) to better understand the pathophysiological mechanisms underlying PCC.

MATERIALS AND METHODS
In this prospective, monocentric study, we analyzed clinical and cerebral blood flow (CBF) data from a cohort of 55 patients who met the WHO diagnostic criteria for Post-COVID condition (PCC) and underwent MRI approximately 11 months after a positive PCR test for SARS-CoV-2. These PCC patients were compared to a matched control group of 36 individuals who had contracted COVID-19 but did not develop PCC. CBF was assessed using arterial spin labeling (ASL), a promising non-invasive technique that provides high spatial resolution for quantifying cerebral blood flow. Additionally, we examined changes in gray matter volume and atrophy using FreeSurfer-based cortical morphometry. We further explored the relationship between regional CBF alterations and clinical symptoms, including cognitive and olfactory function, as well as fatigue.

RESULTS
In our cohort, 59% of PCC patients could not return to their previous level of independence or employment due to symptoms, and 81% reported fatigue on the WEIMuS questionnaire. Conventional MRI showed no evidence of cortical atrophy. While no significant differences in regional CBF emerged after FDR correction, a more explorative threshold (p < 0.005) revealed reduced CBF in the right angular and middle occipital gyri in PCC patients. Fatigue, as assessed by the WEIMuS, was significantly correlated with reduced CBF in the right occipital regions, particularly for physical fatigue, but no associations were found with cognitive or olfactory performance.

CONCLUSION
In PCC patients, fatigue was associated with reduced perfusion in right-sided occipital regions, suggesting a potential pathophysiological basis for this symptom. These findings may also provide an imaging biomarker to aid in the diagnosis of PCC.

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Interestingly, our observation of parieto-occipital hypoperfusion aligns with findings from studies on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [37]. Here, ASL showed a reduced regional CBF at rest within right-hemisphere occipital regions including the inferior occipital gyrus that was correlated with the level of self-reported fatigue [38].

Moreover, a reduced Blood-Oxygenation-Level Dependent (BOLD)-signal as a measure of tissue perfusion in response to a selective attention test has been described in the right medial occipital cortex [39]. The degree of hypoactivation was also associated with outcomes in physical and mental health questionnaires.

In addition to such a reduction of perfusion, voxel-based morphometry revealed reduced grey matter volume in bilateral occipital areas in ME/CFS patients [40] and cerebral proton magnetic resonance spectroscopy detected an increase in choline within the occipital cortex in line with an abnormality of phospholipid metabolism [41].

Spoiler: References

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• 38. Gay CW, Robinson ME, Lai S, O’Shea A, Craggs JG, Price DD, et al. Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses. Brain Connect. 2016;6(1):48–56. doi: 10.1089/brain.2015.0366. pmid:26449441
• 39. Shan ZY, Barnden LR, Kwiatek RA, Bhuta S, Hermens DF, Lagopoulos J. Neuroimaging characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review. J Transl Med. 2020;18(1):335. doi: 10.1186/s12967-020-02506-6. pmid:32873297
• 40. Puri BK, Jakeman PM, Agour M, Gunatilake KDR, Fernando KAC, Gurusinghe AI, et al. Regional grey and white matter volumetric changes in myalgic encephalomyelitis (chronic fatigue syndrome): a voxel-based morphometry 3 T MRI study. Br J Radiol. 2012;85(1015):e270-3. doi: 10.1259/bjr/93889091. pmid:22128128
• 41. Puri BK, Counsell SJ, Zaman R, Main J, Collins AG, Hajnal JV, et al. Relative increase in choline in the occipital cortex in chronic fatigue syndrome. Acta Psychiatr Scand. 2002;106(3):224–6. doi: 10.1034/j.1600-0447.2002.01300.x.